tbuckley/cabot-search huggingface dataset:
Palliative specialty care availability for adults in community oncology practices.
Authors: Tiffany M. Statler, Emily Van Meter Dressler, Heidi D. Klepin, Kathryn E. Weaver, Jennifer Gabbard
Journal: Journal of Clinical Oncology (2022)

e24110 Background: The American Society of Clinical Oncology recommends integration of palliative care in patients with advanced cancer. Studies have shown the availability of palliative care services, especially in outpatient settings, varies widely across practice sites; factors associated with outpatient palliative care clinic availability remain unknown. Our study describes the presence and characteristics of palliative care resources in community oncology practices. Methods: Analyses used data from the 2015 Cancer Care Delivery Research (CCDR) Landscape Assessment of National Cancer Institute Community Oncology Research Program (NCORP) practices (funding support provided by 2UG1CA189824). Oncology practices were surveyed regarding availability of specialty providers and supportive services, including palliative care, as reported by designated CCDR leads. Descriptive statistics describe availability of providers and services, and logistic regression models identify practice characteristics associated with supportive/palliative care specialist availability. Results: 216 non-pediatric exclusive NCORP practice groups were included in analyses. Characteristics are shown in Table. A majority of practices had palliative care specialists (76%), oncology certified nurses (95%), and advance practice providers (80%); 45% had nurse navigators for oncology. 76% of practices had inpatient palliative care consultation services, but only 36% had a dedicated outpatient palliative care clinic. Multivariable analyses demonstrated practices with Medicaid and/or uninsured patient volumes &gt; 25% (Odds Ratio (OR) = 2.5, p = 0.020), more oncology providers (OR = 1.02, p = 0.025), survivorship clinic availability (OR = 2.5, p = 0.005), and who participated in the Quality Oncology Practice Initiative (QOPI) (OR = 2.0, p = 0.039) were significantly more likely to have an outpatient palliative care clinic. Conclusions: Most community oncology practices reported having palliative care specialists, although only a third had a dedicated outpatient palliative care clinic. Newly discovered factors associated with increased odds of having an outpatient palliative care clinic can inform future efforts to expand the availability of outpatient palliative care clinics within community oncology practices.[Table: see text]
A novel pan-RAS inhibitor for malignant peripheral nerve sheath tumors.
Authors: Tariq Arshad
Journal: Journal of Clinical Oncology (2022)

e23531 Background: Malignant Peripheral Nerve Sheath Tumors (MPNST) are a rare but deadly form of sarcoma originating from the Schwann cell compartment. They are usually driven by loss of function of the NF1 tumor suppressor. This can happen spontaneously but is also the cause of disease in the inheritable syndrome of Neurofibromatosis. Neurofibromatosis is a member of the family of genetic diseases known as “Rasopathies” and is one of the most common inherited neurological disorders. NF1 serves as an important negative regulator or GAP for the RAS oncoprotein. Loss of function of NF1 thus results in the upregulation of non-mutant RAS activity and this appears to be a driving event in the disease. Therapeutic options remain poor. An obvious approach to effective treatment would be targeted therapy directed at non-mutant Ras proteins. There are currently no approved pan-RAS inhibitors. We have developed a small molecule pan-RAS inhibitor which binds directly to all forms of RAS. It acts to block the ability of RAS and to bind and signal through its effectors. It is active in vitro and in vivo against multiple models of MPNST. Methods: In silico screening of a virtual compound library was performed to identify an initial candidate inhibitor. Iterative rounds of Medicinal Chemistry informed by structural modeling and bioassay in 3D vs 2D growth assays were performed to identify an enhanced activity derivative. Target binding was confirmed by Microscale Thermophoresis and NMR. RAS/RAF complex status was measured by co-immunoprecipitation of the endogenous proteins. Ras signaling was assayed by Western analysis of Phospho-ERK and RAL-GTP pull down assays. In vitro activity was measured using 3D soft agar assays. In vivo activity was measured by ip or po administration against MPNST pdx systems. Results: The current lead, designated RAS-F binds all three main isoforms of RAS at low uM kd and modulates the RAS effector domain in NMR studies. It suppresses RAS signaling pathways in transient assays and suppresses MPNST tumor cell growth in soft agar with IC50s ̃ 250nM. It suppresses MPNST pdx growth. Conclusions: We have developed a pre-clinical pan-RAS inhibitor that is active in vitro and in vivo against MPNST cancer models. The agent also has potential uses against non-tumor manifestations of Neurofibromatosis such as Plexiform and Cutaneous neurofibromas. Funding: NIH 5U01HL127518-03, Kentucky Lung Cancer Research Program CDMRP NF180094 (GJC). Qualigen Therapeutics LLC (GJC, JOT).
Efficacy of the combination of tamsulosin and methylprednisolone on postoperative early pain and outcomes after uncomplicated and unstented ureteroscopic lithotripsy. A randomized controlled trial
Authors: P. Gupta, R. Manikandan, L.N. Dorairajan, S.K. Sreenivasan, S. Kalra, A. Jagannath, S. Hota
Journal: European Urology (2022)
Robust SARS-CoV-2-specific and heterologous immune responses in vaccine-naïve residents of long-term care facilities who survive natural infection
Authors: Gokhan Tut, Tara Lancaster, Megan S. Butler, Panagiota Sylla, Eliska Spalkova, David Bone, Nayandeep Kaur, Christopher Bentley, Umayr Amin, Azar T. Jadir, Samuel Hulme, Morenike Ayodel, Alexander C. Dowell, Hayden Pearce, Jianmin Zuo, Sandra Margielewska-Davies, Kriti Verma, Samantha Nicol, Jusnara Begum, Elizabeth Jinks, Elif Tut, Rachel Bruton, Maria Krutikov, Madhumita Shrotri, Rebecca Giddings, Borscha Azmi, Chris Fuller, Aidan Irwin-Singer, Andrew Hayward, Andrew Copas, Laura Shallcross, Paul Moss
Journal: Nature Aging (2022)

Abstract We studied humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 152 long-term care facility staff and 124 residents over a prospective 4-month period shortly after the first wave of infection in England. We show that residents of long-term care facilities developed high and stable levels of antibodies against spike protein and receptor-binding domain. Nucleocapsid-specific responses were also elevated but waned over time. Antibodies showed stable and equivalent levels of functional inhibition against spike-angiotensin-converting enzyme 2 binding in all age groups with comparable activity against viral variants of concern. SARS-CoV-2 seropositive donors showed high levels of antibodies to other beta-coronaviruses but serostatus did not impact humoral immunity to influenza or other respiratory syncytial viruses. SARS-CoV-2-specific cellular responses were similar across all ages but virus-specific populations showed elevated levels of activation in older donors. Thus, survivors of SARS-CoV-2 infection show a robust and stable immunity against the virus that does not negatively impact responses to other seasonal viruses.
ADVL1514, a phase 1 study of ABI-009 (nab-sirolimus) in pediatric patients with recurrent or refractory solid tumors, including CNS tumors as a single agent and in combination with temozolomide and irinotecan: A Children’s Oncology Group pediatric early-phase clinical trial network study.
Authors: Stuart Cramer, Elizabeth Ann Gilger, Susan Burlingame, Olga Militano, Xiaowei Liu, Charles G. Minard, Alyssa Terry Reddy, Stephan D. Voss, Stacey L. Berg, Joel M. Reid, Elizabeth Fox, Brenda Weigel
Journal: Journal of Clinical Oncology (2022)

10022 Background: nab-Sirolimus (formerly know ABI-009 and nab-rapamycin) is a novel human albumin-bound preparation of sirolimus, a potent mTOR inhibitor. We report results of a Phase I study of ABI-009 alone and in combination with irinotecan and temozolomide in children with relapsed/refractory solid or CNS tumors. Methods: Patients (age 1-21 years) with relapsed/refractory solid or CNS tumors were eligible. Using a rolling 6 design, ABI-009 was administered intravenously as a single agent on Days 1 and 8 of cycle 1 (cycle = 21d), then subsequent cycles ABI-009 was administered in combination with temozolomide (125 mg/m 2 /dose, maximum 250 mg/dose) orally once daily x 5 on Days 1-5 and irinotecan 90 mg/m 2 /dose orally once daily x 5 on Days 1-5. Three dose levels (DL) of ABI-009 were investigated (DL1: 35mg/m 2 /dose, DL-1: 20mg/m 2 /dose, and DL-2: 15mg/m 2 /dose). The maximum tolerated dose (MTD) or Recommended Phase 2 Dose (RP2D) was established based on dose limiting toxicity (DLT) observed during Cycle 1 and 2. At the RP2D, additional patients were enrolled for pharmacokinetics (PK). Results: 33 patients were enrolled (32 eligible and 1 ineligible); 11 did not experience DLT but were not evaluable for toxicity due to progressive disease or physician decision to discontinue protocol therapy prior to completion of cycle 2; 17 [median age 13 (2-20) years] were evaluable for determination of MTD during dose escalation, 6 were enrolled on the PK cohort, of which 3 were evaluable to toxicity. At DL1, 2/5 patients experienced DLT (thrombocytopenia during cycle 1 (n = 1) and cycle 2 (n = 1)); at DL-1, 2/6 patients experienced DLT (thrombocytopenia in cycle 1); at DL-2, 1/6 patients experienced DLT (thrombocytopenia in cycle 1). PK expansion enrolled at DL-2 and 1/3 participants evaluable for toxicity had a DLT (mucositis). Overall, at DL-2, 2/9 patients (22%) had DLT. One patient with Ewing Sarcoma had a partial response and remained on study for 35 cycles; Patients (one each) with Ewing Sarcoma, Wilms Tumor, and Pineoblastoma had stable disease, ranging from 3-6 cycles. Conclusions: Thrombocytopenia was dose limiting for ABI-009 alone and in combination with temozolomide and irinotecan. The MTD for ABI-009 is 15mg/m 2 /dose days 1 and 8 in combination with 5 daily doses of temozolomide 125 mg/m 2 /dose and oral irinotecan 90 mg/m 2 /dose. One patient had a partial response, 3 patients had prolonged stable disease. Pharmacokinetics and pharmacodynamics are pending and will inform future trials. Clinical trial information: NCT02975882.
Interspecies commensal interactions have nonlinear impacts on host immunity
Authors: Tyler A. Rice, Agata A. Bielecka, Mytien T. Nguyen, Connor E. Rosen, Deguang Song, Nicole D. Sonnert, Yi Yang, Yiyun Cao, Varnica Khetrapal, Jason R. Catanzaro, Anjelica L. Martin, Saleh A. Rashed, Shana R. Leopold, Liming Hao, Xuezhu Yu, David van Dijk, Aaron M. Ring, Richard A. Flavell, Marcel R. de Zoete, Noah W. Palm
Journal: Cell Host & Microbe (2022)
Correlation of urine loss after catheter removal and early continence in men undergoing radical prostatectomy
Authors: B. Hoeh, M. Wenzel, C. Humke, C. Wittler, J.L. Hohenhorst, M. Volckmann-Wilde, J. Köllermann, T. Steuber, M. Graefen, T. Derya, P. Karakiewicz, A. Becker, L.A. Kluth, F.K.H. Chun, P. Mandel
Journal: European Urology (2022)
Therapeutic implications of mutations in high grade serous ovarian carcinoma when evaluated by race.
Authors: Ruchi Garg, Julian C. Schink, Barbara Buttin, Julia Andrea Elvin, Natalie Godbee, Amber Moran, Vicki Doctor, Bradford A. Tan, Judy Sequeria, John H. Farley, Maurie Markman
Journal: Journal of Clinical Oncology (2022)

e17590 Background: Individualizing oncologic treatment by using precision oncology techniques that allow for detection of genomic alterations (GA) has become critical. We present an analysis of comprehensive genomic profiling (CGP) of a large series of high grade serous ovarian carcinoma (HGSOC) patients assayed in a nationwide cancer network. Racial disparities in genomic alterations may assist in better targeting therapies, predicting drug resistance, and potential germline mutations. Methods: 312 patients with HGSOC underwent CGP with hybrid capture on tumor tissue for treatment decision-making between 01-2013 to 06-2021. Clinically relevant genomic alterations (CRGA) were reported as targetable marker. Statistical analysis performed with Fisher Exact test. Results: Median age was 55 years (range, 23-81), 71.2% were White, 16.4% were Black, 3.9% were Hispanic, and 1.3% were Asian. GA were identified in 98.7% (308/312) of these patients. TP53 mutations were present in 286 of 312 patients (91.7%) and interestingly, while not statistically significant (p = 0.06) was present in 98% of black women and 89.2% of white women. BRCA1 mutation was present in 14.4% of white women and in 17.6% of black women. BRCA2 mutation was present in 9.9% of white women and 9.8% of black women. Several interesting mutations were identified, see table below. Conclusions: In this 312-patient series of women with HGSOC, we note several prominent mutations in the tumors. While not statistically significant, there is a trend of larger number of poorer prognostic mutations in black women including p53, KRAS and CCNE1. Some studies have found the amplification of CCNE1 and mutation of homologous recombination repair genes to be mutually exclusive in HGSOC which may compel us to find other therapeutic interventions than the PARP inhibitors for these patients.[Table: see text]
Correlative analysis to define patient profiles associated with manufacturing and clinical endpoints in relapsed/refractory multiple myeloma (RRMM) patients treated with idecabtagene vicleucel (ide-cel; bb2121), an anti-BCMA CAR T cell therapy.
Authors: Julie Rytlewski, Jaymes Fuller, David R. Mertz, Ciara Freeman, Salomon Manier, Nina Shah, Timothy Brandon Campbell
Journal: Journal of Clinical Oncology (2022)

8021 Background: The anti-BCMA autologous CAR T cell therapy ide-cel has achieved deep and durable responses in RRMM patients (Munshi, N Engl J Med 2021). Prior studies have described the correlation between patient characteristics and clinical outcomes from CD19 CAR T cell therapy (Finney, J Clin Invest 2019; Fraietta, Nat Med 2018). We sought to define patient profiles correlated with manufacturing and clinical endpoints in RRMM patients treated with ide-cel in clinical trials using unsupervised clustering and multivariate machine learning across multiple key variable domains. Methods: Clinical and manufacturing data were harmonized across 164 RRMM patients treated with ide-cel in KarMMa (NCT03361748) and KarMMa-2 cohort 1 (NCT03601078). Based on individual multivariate importance, 10 selected peripheral blood mononuclear cell (PBMC), drug product (DP), and in-process cell growth variables were used to define patient clusters. Random forest classifiers were generated to identify patient characteristics associated with manufacturing and clinical endpoints. Wilcoxon rank sum and Kruskal-Wallis tests were used to compare 2 and 3+ categorical groups; Cox proportional hazards were used to compare groups with time-to-event data. Results: Using an unsupervised method, 4 patient clusters were identified that represented 10%, 57%, 15%, and 18%, respectively, of the total 164 patients. Cluster 4 was the most favorable and was characterized by a higher frequency of T cells in PBMCs; increased T-cell size during manufacturing; higher DP T-cell transduction, potency, and vector copy number; and ultimately a &gt; 3-fold higher CAR T cell yield compared with the least favorable cluster 1. Cluster 2 contained most patients and was associated with intermediate manufacturing endpoints. Patients in cluster 4 had a higher complete response rate, longer progression-free survival, and were defined by lower tumor burden, higher absolute lymphocyte count (ALC), and longer washout period after alkylator treatment, among others (Table). Conclusions: The current study identified patient profiles in RRMM using accessible laboratory or medical history data that correlated with longitudinal outcomes. These findings may inform patients likely to achieve improved outcomes with CAR T cell therapy. Clinical trial information: NCT03361748. [Table: see text]
Assessment of antitumor effect of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in subcutaneous xenografts of A-549 tumor cell culture.
Authors: Ekaterina A. Lukbanova, Elena A. Dzhenkova, Marina A. Engibaryan, Yulia V. Ulianova, Elena G. Goncharova, Viktoriya L. Volkova, Ekaterina Fedorovna Komarova, Mamuka V. Bauzhadze, Elizaveta Komarova, Irina V. Pustovaya, Natalia A. Chertova, Astanda K. Gvaramiya, Maria A. Cherkes, Mary L. Maldonado, Nataliya Shevchenko, Maria V. Mindar
Journal: Journal of Clinical Oncology (2022)

e20520 Background: The aim of the study was an assessment of antitumor effect of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone for subcutaneous xenografts of A-549 lung tumor cells in immunodeficient Balb/c Nude mice. Methods: 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone is a new compound in the series of 2-quinoline-2-yl-1,3-tropolone derivatives. The study included 50 immunodeficient Balb/c Nude mice divided into 5 groups depending on the dosage of the studied substance (0.0055; 0.055; 0.55 and 2.75 mg/g). The A-549 cells of lung cancer were used as the xenograft. Antitumor effect of tropolone was evaluated by the inhibition of tumor growth (ITG%) and the index of tumor growth (I). The experiment lasted for 36 days starting from the first administration of substances. Results: Indicators of the average tumor volume on day 36 of the experiment in experimental groups 1, 2, 3 and 4 and in the control group were 678.9; 952.3; 1746.4; 2150.8 and 2729.5 mm3, respectively. The indices of tumor growth in groups 1, 2, 3 and 4 were statistically significantly lower than in group 5 (controls) starting from days 15, 21, 21 and 24, respectively, and until the end of the experiment. Maximal differences between groups 1 and 5 were observed on days 33 and 36 – by 3.7 (p = 0.01) and 4.1 (p = 0.003) times, respectively. Antitumor effect of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone demonstrated by the study could be associated with various mechanisms. For example, its closely related compound – hinoktiol, according to numerous studies, has a cytotoxic effect associated with stopping the cell cycle, induction of apoptosis, DNA damage, and autophagic death of tumor cells. Conclusions: The study demonstrated statistically significant differences in xenograft volumes between all experimental groups and the control group. 2.75 mg/g of mouse weight was the most effective dosage of the studied compound leading to a slow decrease in tumor growth rates and a decrease in the volumes of subcutaneous xenografts.
Definition and predictors of upgrading at final pathology in prostate cancer patients undergoing mri-targeted and systematic biopsies: Results from a large, multi-institutional series
Authors: G. Gandaglia, E. Mazzone, G. Ploussard, G. Marra, M. Valerio, R. Campi, A. Mari, A. Minervini, S. Serni, M. Moschini, A. Marquis, J.-B. Beauval, A. Rakauskas, F. Sessa, R.C.N. Van Den Bergh, R-G. Rahota, T. Soeterik, M. Roumiguié, L. Afferi, J. Zhuang, H. Guo, A. Mattei, P. Gontero, F. Montorsi, A. Briganti
Journal: European Urology (2022)
Medication use among lung cancer patients before and after initiating immune checkpoint inhibitors: A population study.
Authors: Chuchu Mei, Amy Yang, Amy L Shaver, Nikita Nikita, Joshua Banks, Scott W. Keith, Grace L. Lu-Yao
Journal: Journal of Clinical Oncology (2022)

e21119 Background: Polypharmacy is an independent prognostic factor in older patients with lung cancer treated with immune checkpoint inhibitors (ICIs). Previous studies have shown that steroids, opioids, proton pump inhibitors, fluoroquinolone are associated with worsening overall survivals for lung cancer patients. The prevalence of drug use among lung cancer patients using ICIs is understudied. Methods: The study population consisted of older adults (aged 65 years or older) diagnosed with lung cancer from January 1, 2011, to December 31, 2016, in the Surveillance, Epidemiology, and End Results–Medicare linked database. Patients with a diagnosis of lung cancer and a claims record showing nivolumab plus ipilimumab combination therapy or anti–PD-1 therapy (ie, pembrolizumab or nivolumab) as their ICI prescribed were included in the analyses. Index date was defined as the date of first dose of ICIs. We examined medication usage within 90 days prior and after index date. Drug categories were classified, by mechanism of action from Lexicomp®, using Medicare Part D Drug event generic name. Descriptive analysis was used to show the percentage of concurrent drug usage for each drug category. McNemar test was used to compare the drug use prevalence before and after index day. Results: There are 669 patients in the study (male [48.56%], 65–74-year-old [67.10%]). Usage of steroids (89.09%), opioids (87.89%) was high before ICIs. Significant decreases were observed between before and after the index day for most prescribed drug categories, including anti-psychotics (-62.94%, p &lt; .0001). But the use of thyroid products (35.83%, p &lt; .0001) increased in usage after starting ICIs. Conclusions: To our knowledge, this is the first population-based study to quantify concurrent medication use amongst lung cancer patients undergoing immunotherapy. This study suggests the polypharmacy decreased significantly after initiation of ICIs. Future studies are required to investigate the reasons for the changes in medication use and increased utilization of thyroid products.[Table: see text]
Data independent acquisition mass spectrometry in relation to potential diagnostic and prognostic biomarkers for high-grade serous ovarian cancer.
Authors: Sunghyun Huh, Se Ik Kim, Jieun Park, Kyerim Choi, Hyunjee Jang, Sang-Won Lee, Daehee Hwang, Myeong-Hee Yu, Hyun Hoon Chung, Un-Beom Kang
Journal: Journal of Clinical Oncology (2022)

e17564 Background: Ovarian cancer (OC) is one of the most common causes of cancer-related death among women worldwide. High-grade serous ovarian cancer (HGSOC) represents the major OC histological type, and challenges associated with its early detection and prediction of clinical outcomes significantly contribute to the high prevalence and poor prognosis of OC. Lack of reliable biomarkers further exacerbates the low survival rate of patients with HGSOC. Methods: In this study, we performed liquid chromatography data independent acquisition tandem-mass spectrometry (LC-DIA-MS/MS) experiments on depleted serum samples [26 HGSOC cases, 24 healthy controls (HCs)] to identify potential diagnostic and prognostic biomarkers for HGSOC. Results: A total of 1,148 proteins were identified in all samples combined, representing one of the largest quantifications in the serum proteome of OC to date. Among them, 122 proteins showed differential expressions between the serum proteome of HGSOC patients and HCs, including 109 up- and 14 down-regulated proteins in HGSOC. These potential diagnostic biomarkers were involved in the pathways related to immune response, TGF- β and IGF signaling, and lipid metabolism. Moreover, we performed Kaplan-Meier survival analysis on the HGSOC patients with and without recurrence, and identified several potential prognostic biomarkers highly associated with progression free survival (PFS). Using independent cohort samples, we validated the expression levels of HGSOC serum biomarker candidates using targeted proteomics approaches (MRM and PRM). In vitro functional assays revealed that some of these biomarkers may play an essential role in cancer cell migration and proliferation in HGSOC. Conclusions: In summary, our LC-DIA-MS/MS analysis of the HGSOC serum proteome successfully identified novel diagnostic and prognostic biomarkers for HGSOC, some of which were experimentally shown to have functional relevance to the pathophysiology of OC.